tbuckley/cabot-search huggingface dataset:
Incidence of low volume metastases after retrospective ultrastaging of patients with early stage, node negative cervical cancer and receipt of post-operative adjuvant therapy.
Authors: Annalyn Welp, Michael Crawford, Rachel O'Brien, Stephanie Sullivan, Linda R. Duska
Journal: Journal of Clinical Oncology (2023)

e17506 Background: Nodal positivity directs receipt of adjuvant post-operative therapy in early stage cervical cancer; the significance of low-volume metastases (LVM) is unclear. We hypothesized patients with early stage cervical cancer with high risk factors on pathology and negative nodes would have a higher incidence of LVM on retrospective ultrastaging. Methods: This retrospective cohort study collected clinicopathologic data via chart review on early stage cervical cancer patients treated at our institution from January 2011 - June 2021. The study was approved by the IRB. Inclusion criteria included patients &gt;18 years old who underwent a radical hysterectomy/trachelectomy with pathology-proven negative nodes who went on to be recommended for post-operative adjuvant therapy, due to factors defined under Sedlis or Peters criteria. Patients were excluded for rare histology or prior pelvic radiation. Resected nodes were ultrastaged, performed by 4 re-cuts at 20 microns on each lymph node staging, stained with H&amp;E and one level with CK AE1/AE3 to identify presence of any LVM. Analysis was performed via descriptive statistics with Microsoft Excel. Results: 199 patients were treated with radical hysterectomy between 2011-2021; 20 met study criteria. The average age at diagnosis was 51 years: 65% Caucasian, 25% Black, 10% Latino. 75% had Squamous cell carcinoma, 85% (n=17) of the cohort were a 2009 FIGO pathologic Stage 1B. 35% of the cohort underwent a minimally invasive hysterectomy. Tumor size varied: 25% (n=5) of tumors were less than 2 cm, 35% (n=7) of tumors measured greater than or equal to 2 cm, 30% (n=6) measured greater than or equal to 3 cm, and 10% (n=2) measured greater than or equal to 4 cm. Lymphovascular space invasion was noted in 75% (n=15) of samples. Superficial stromal invasion was noted in 5% (n=1), deep stromal invasion was noted in 65% (n=13). 5% (n=1) of patients had parametrial invasion, and 5% (n=1) had positive margins. A full bilateral pelvic lymphadenectomy was performed on every patient, with 245 nodal blocks ultrastaged. 80% (n=16) received adjuvant therapy: 3 chemoradiation, 13 radiation, 4 declined. LVM was identified in 5% (n=1) patients; a macrometastases was identified as missed in the initial pathologic evaluation of another. 10% (n=2) patients developed recurrence, one at the pelvic brim and one distant (lung). The patient with the newly identified LVM received adjuvant radiation, and developed recurrence at the pelvic brim. Conclusions: The results of this small study suggest traditional “high risk” factors in surgically managed cervical cancer is associated with positive ultrastaged nodes in 5% of cases. This finding suggests that utilization of sentinel node identification with associated ultrastaging will accurately identify patients who will benefit from adjuvant therapy.
Incidence of palliative care consultations in end-of-life care among patients with pancreatic cancer in the US.
Authors: Kaushik Gokul, Zidong Zhang, Divya S. Subramaniam
Journal: Journal of Clinical Oncology (2023)

e16302 Background: Integration of palliative care in the treatment plan for a variety of diseases has been shown to improve quality of life, reduce aggressive interventions, and reduce cost burdens. This study aimed to explore the incidence of palliative care consultations in pancreatic cancer patients and determine its influence on the utilizations of aggressive interventions towards end of life. Methods: We conducted a retrospective study using a de-identified national Electronic Health Record (EHR) database, which captured deceased patients between January 1, 2000 to December 21, 2018, with a diagnosis of pancreatic cancer. Clinical history from 0-6 months prior to death was examined for the presence of a palliative care consultation (PCC) encounter. Aggressive interventions of interest, namely emergency department visits, chemotherapy, and ICU admissions, were identified and recorded in both the last six months and the last month of life. Demographic variables such as age, gender, race, and location were also considered during analysis. The PCC group and non-PCC group were compared using the Whitney U-test and Chi-squared test. Results: 2,883 deceased patients with PanCa were identified. However, 2,025 of these patients did not receive PCC in the last six months of life. The average age of death was greater at 70.5 years within the PCC group as compared to 68.9 years within the non-PCC group. This difference was statistically significant. In the last 6 months prior to death, 14.1% of patients overall had chemotherapy. The proportion of patients having chemotherapy was greater among the PCC patients compared to those not (22.4% vs 10.6%). Compared to those who did not receive PCC, patients who had PCC in the end of life were also more likely to be hospitalized (81.1% vs 38.2%), visit emergency departments (45.1% vs 23.7%) and stay in the ICU (14.1% vs 4.0%). In the last 30 days of life, trends were similar. Within PCC, 3.4% had chemotherapy while 1.3% had chemotherapy in the non-PCC group. As far as hospitalizations go, among patients with PCC, 51.3% were hospitalized compared to 15.5% hospitalizations in non-PCC. In patients who had PCC, 14.8% had at least one emergency department visit while 4.8% of patients in the non-PCC group had at least one emergency department visit. Lastly, ICU stays showed a similar trend to the previous interventions. In PCC patients, 7.9% had at least one ICU stay while only 1.5% of patients had one in the non-PCC group. Conclusions: Our study found that less than 30% of patients with PanCa received PCC at the end of life. Findings show an urgency to increase awareness and utilization of PCC for such patients. Interventions should be developed to address this urgency to help improve quality and efficiency of care. Future studies will also identify barriers and facilitators in implementing PC and consultation for patients with PanCa.
Effect of change in ECOG performance status at diagnosis and relapse in patients with acute myeloid leukemia.
Authors: Michelle Zhang, Carole Shaw, Katie Russell, Anna B. Halpern, Jacob Appelbaum, Paul Hendrie, Cristina Maria Ghiuzeli, Roland B. Walter, Mary-Elizabeth M. Percival
Journal: Journal of Clinical Oncology (2023)

e19007 Background: ECOG performance status (PS) is often utilized in treatment decision-making for patients with acute myeloid leukemia (AML). Patients with relapsed or refractory (R/R) disease have a particularly poor prognosis and require complex treatment decisions that weight patient preference, disease risk and PS. Currently, limited data exist on changes in performance status from initial diagnosis to the time when R/R AML is found. It would be interesting to characterize whether patients with R/R AML have worse performance status due to progression of disease or stable or improved performance status after initial therapy. Given there are additional factors such as induction chemotherapy that impact performance status at R/R disease, we were also interested in characterizing the association of PS in R/R AML with short and long term survival. Methods: We utilized an institutional database from University of Washington/Fred Hutchinson Cancer Center to retrospectively identify patients with AML or other high-grade myeloid neoplasms (≥10% blasts) who received both induction and salvage chemotherapy between January 1, 2008 through December 1, 2021. Patients with missing performance status at R/R were excluded. Salvage treatment was divided into high (cytarabine greater than 1g/m 2 /dose), intermediate (7+3 or similar), or reduced intensity (i.e., hypomethylating agents). The McNemar test was used for matched-pair analysis of PS at two timepoints. The Kaplan-Meier method was used for overall survival (OS). Univariate and multivariable linear regression models were used to evaluate associations with 4 week survival. All statistical analyses were performed using R 4.2.1 (2022). Results: Of the patients identified (n = 614), only patients with PS documented at R/R (n = 51) were included in the analysis (baseline characteristics in Table 1). No significant change was identified in PS at diagnosis versus R/R (PS≤1 66.7% vs 70.6%, p = 0.80). Better performance status (PS≤1) at R/R was correlated with improved OS (11.4 months vs 2.33 months, p = 0.003). The 4-week unadjusted mortality rate was 8.5% for patients with PS≤1, and 33.3% for patients with PS &gt; 1 (p = 0.04). Poor performance status (PS &gt; 1) at R/R was associated with significantly increased 4 week mortality (OR 5.5, 95% CI 1.2-30.9), even after adjustment for age and ELN2017 risk (OR 6.2, 95% CI 1.1-41.3). When OS was further stratified by chemotherapy intensity, patients with PS≤1 (n = 36) treated with high intensity chemotherapy (n = 22) had improved OS (14.1 vs 4.3 months, p = 0.007). Conclusions: PS tends to be stable at R/R disease, and poor PS is associated with very poor survival. Further work is needed to characterize the patients with R/R AML who benefit from intensive re-induction chemotherapy.
Response and re-treatment response to immune checkpoint inhibitor treatment in advanced cervical cancer: A follow up study.
Authors: Jennifer Wolf, Yiqing Xu
Journal: Journal of Clinical Oncology (2023)

e17516 Background: Single agent checkpoint inhibitor immunotherapy (CII) was approved in June 2018 for second line treatment for metastatic cervical cancer after failure of platinum-based chemotherapy. Clinical trials recommended 2 years of treatment, however the optimal duration of treatment, outcome after stopping treatment and response after re-initiation of immunotherapy is still largely unclear. Methods: A cohort of 10 patients who were started on CII before September 31, 2019, with an initial analysis published in July 2021 were eligible. We performed an updated review of the duration of response, outcome off treatment after 2 years, and outcome after re-initiation of CII. Results: The current median follow up is 40 months (range, 2.0-50.8 months), 4 patients did not respond to treatment and have passed away, while six patients remain alive. The previous report showed 7 responders, with 3 complete responses (CR) at a median follow up of 20.7 m. With prolonged treatment, 6 patients achieved CR or stable minimal disease. After more than 2 years of treatment, 2 continued treatment for 39m and 50 m. Among the 4 patients who stopped treatment, 2 of them are 18 m and 20 m off treatment and remain no evidence of disease. Another 2 patients developed asymptomatic recurrence detected on surveillance CT (at 9 m and 12 m respectively), both with small volume of disease in the retroperitoneal and pelvic lymph nodes. They were both re-initiated on CII, and showed a CR and partial response (PR) respectively, on 3-6 month follow up CT scans, now 11.7 m and 3.5 m on treatment. A median PD-L1 combined expression score (CPS) was similar between responders (n=6) (20) and non-responders (26) (n=4) in the entire cohort overall, and was 83 in the group of patients who discontinued treatment after 2 years and have been without evidence of disease since (n=2). Conclusions: Patients who respond to immune checkpoint inhibitors may have durable response off treatment and may respond again to re-treatment in the event of recurrent disease. Our limited data suggest that providers can use CPS to aid in decision making. [Table: see text]
A cross-sectional study of 73,390 women without ovarian cancer and the effect of age and benign gynecological diseases on serum CA125 levels.
Authors: Chenchen Zhu, Shan Jiang, Bei Yao, Liang Chen, Buyun Liu, Hanyuan Liu, Lili Qian, Qianqian Yan, Yi Liu, Cheng Peng, Ying Zhou
Journal: Journal of Clinical Oncology (2023)

e17500 Background: As an important tumor marker for follow-up and prognosis of ovarian cancer, CA125 is not suitable as a screening indicator due to its frequent elevation in many physiological or pathological condition, thus women are often puzzled by unaccountably elevated levels of CA125. While we have known that the CA125 level is differed by age and benign gynecological diseases, the specific trend of CA125 level changes is still not clear. We hope that this study will contribute to a more accurate and individual interpretation of CA125 by evaluating the baseline levels of CA125 in healthy women of different ages and analysis the association between benign gynecological diseases and CA125 level. Methods: This was a cross-sectional study enrolled 73390 women without ovarian cancer from January 2016 to December 2021 in three health examination centers. We have assessed the distribution of CA125 levels in different age groups and analyzed the variation trend of CA125 levels by age among women with normal ultrasonic results, as well as performed the correlation analysis between several benign gynecological diseases and CA125 levels. Results: 55422 women with normal ultrasonic results and CA125 level &lt;200U/mL were included in the analysis of variations in CA125 depending on age. We observed CA125 levels were linearly associated with age (R 2 =0.0503, p&lt;0.0001). Using the group &lt;30 years as a baseline, average CA125 levels decreased by 3.4%, 10.1%, 42.6%, 40.5%, 31.8%, and 20.3% by every 10 years. With the increase of age, the downward trend of CA125 began to reverse at the age of 60, and it showed significantly difference between each adjacent subgroup (p&lt;0.05). 8630 women were selected with abnormal ultrasonic results, we observed that CA125 was lower in women with uterine effusion, higher in endometrial hyperplasia, endometrial polyps, hydrosalpinx, ovarian cyst, adenomyosis and uterine fibroids. Age and all those diseases demonstrated possible associations (p&lt;0.05) with CA125 levels ≥35U/ml in univariable logistic regressions. Multivariable analysis identified that ovarian cyst (p&lt;0.001), adenomyosis (p&lt;0.001) and uterine fibroids (p=0.018) were still significantly associated with abnormal CA125 level. Conclusions: With the increase of age, CA125 level generally showed a downward trend, but there is a slight increase in CA125 after age 60. Ovarian cyst, adenomyosis and uterine fibroids demonstrated significant associations with abnormal CA125 level. [Table: see text]
Phase II study evaluating the efficacy of niraparib and dostarlimab (TSR-042) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients.
Authors: Olga Zamulko, Vidhya Karivedu, Muhammad Kashif Riaz, Ilaina Monroe, Audrey Romano, Rachel Mulanda, Nicky Kurtzweil, Allison Forsythe, Casey Allen, Nusrat Harun, Trisha M. Wise-Draper
Journal: Journal of Clinical Oncology (2023)

6046 Background: Patients with recurrent and/or metastatic (R/M) HNSCC have poor overall survival. Immune checkpoint inhibitors (ICIs), specifically programmed death-1 (PD-1) inhibitors, result in durable responses in R/M HNSCC but &lt;20% benefit. Tumor mutational burden (TMB) correlates with ICI response. DNA pathway repair mutations have been reported in 17% of sporadic HNSCC and are associated with higher rates of TMB. Poly (ADP-ribose) polymerase (PARP) inhibition has demonstrated efficacy as a single agent in cancers with a DNA repair defect. We tested the combination of PARP inhibitor (niraparib) with the PD-1 inhibitor (dostarlimab) in R/M HNSCC patients (NCT04313504) with funding support from Tesaro/GSK. Methods: Patients with R/M HNSCC who failed at least one line of prior treatment including a PD-1 inhibitor and for whom no surgical or radiation curative options existed were eligible for the study. Patients received niraparib (200 mg daily) beginning one week prior to initiation of dostarlimab (500 mg q3wks x4 followed by 1000 mg q6wks). The primary endpoint was overall response rate (ORR) including complete response (CR), partial response (PR) and stable disease (SD) using RECIST v1.1. Fourteen patients were planned for the first stage and 10 additional patients for the second stage if ≥8 patients had a confirmed response. Safety was evaluated by CTCAE v5.0. Tumor PD-L1 immunohistochemistry was performed with 22c3 antibody and reported as combined positive score (CPS). TMB was considered high if ≥10Mut/Mb. Results: Ten of 24 planned patients were enrolled. Of the first 10 patients, 8 patients were evaluable by imaging and 1 patient clinically progressed on exam. Of the 9 evaluable patients, there were 0 CR, 1 PR, 1 SD, and 7 with progressive disease (PD). The trial was ended early for futility as it was not possible for at least 8 out of 14 patients to develop response. The patient with a PR remains on treatment past 24 months, was PD-L1 positive, had low TMB and no DDR deficiency. All patients had previously failed a PD-1 inhibitor. One patient had high TMB, 2 patients had a DDR, and 6 patients were PDL1 positive but 2 patients had insufficient tissue or indeterminate results for sequencing. Grade ≥ 3 adverse events occurred in 70% of patients with most common being hypertension (20%), hyponatremia (20%), and lung infection (20%). Conclusions: PARP-1 inhibition and PD-1 inhibition combined does not appear to enhance response over PD-1 inhibitor alone in R/M HNSCC who had previously failed PD-1 inhibitor treatment. However, a more focused population including those with DNA damage response (DDR) mutations and PD-1 treatment naïve may benefit. Clinical trial information: NCT04313504 .[Table: see text]
Artificial intelligence (AI) analysis of tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&amp;E) slides to explore immune phenotypes in papillary thyroid cancer.
Authors: Myungwoo Nam, Liam Il-Young Chung, Leeseul Kim, Gahee Park, Sukjun Kim, Sanghoon Song, Chan-Young Ock, Young Kwang Chae
Journal: Journal of Clinical Oncology (2023)

6100 Background: Different biomarkers have been discovered to predict response to immunotherapy but the variability of response exists. TILs are a potential biomarker as infiltration of CD8+ T cells in the tumor microenvironment(TME) was related to treatment response to PD-1 blockade. Advanced well-differentiated papillary thyroid cancer(PTC) has limited standard-of-care treatment options and can exhibit a poor prognosis when exhausted. Our study aimed to classify the TME of PTC according to TILs. Methods: Using the TCGA PTC data, samples were classified into three immune phenotypes (immune-’desert’, immune-’excluded’, and ‘inflamed’) based on peri-tumor lymphocyte density from analysis of H&amp;E slides using an AI model(Lunit SCOPE). Immune and stromal cell infiltration was inferred using xCell. Cytolytic scores(CYT) and thyroid differentiation scores(TDS) were calculated using mRNA expression. Results: Total of 383 samples were included. Immune phenotype analysis showed 183(47.7%) ‘desert’, 133(34.7%) ‘excluded’, and 67(17.4%) ‘inflamed’. Median age at diagnosis was the lowest in ‘inflamed’(inflamed 41.5 vs excluded 47 vs desert 50, p = 002). TNM stages were as follows in the order of stages 1 to 4: inflamed 49/4/8/3, excluded 64/13/32/16, and desert 86/28/40/19. BRAF V600E mutation was most prevalent in ‘excluded’(97/133, 72%), followed by ‘inflamed’(32/67, 47.7%) and ‘desert’(51/183, 27.8%). CYT was the highest in ‘inflamed’(median: inflamed 186 vs excluded 53 vs desert 39, p &lt; 0.001). TDS was the highest in ‘desert’(median: inflamed -0.3 vs excluded -0.69 vs desert 0.73, p &lt; 0.001). The 6 cell types with the most statistically significant difference in infiltration were activated dendritic cells(aDCs), DCs, B cells, epithelial cells(EpCs), CD8+ central memory T cells, and CD4+ memory T cells. The ‘inflamed’ showed the highest median value for all of these cells except EpCs. The cells with the highest median value in ‘excluded’ included EpCs, sebocytes, and immature DCs. The cells with the highest median value in ‘desert’ were lymphatic endothelial cells(ECs), ECs, and osteoblasts. Three immune phenotypes were associated with differential outcomes in disease-free survival(log-rank for trend, p-value = 0.01). There was no difference in overall survival. Conclusions: Our results suggest that 15% of PTC can have immune features which were related to a higher rate of response to immunotherapy across different tumor types. A previous study showed that PTC with a low TDS or BRAF V600E mutation is related to increased immune response indices. In our study, TDS or BRAF V600E mutation status could not distinguish the ‘inflamed’ from other phenotypes. This suggests that immune phenotype classification through TILs can provide distinct information about the TME of PTC.
Indirect treatment comparison (ITC) of momelotinib (MMB) vs fedratinib (FED) safety in patients (pts) with myelofibrosis (MF).
Authors: Lucia Masarova, Srdan Verstovsek, Francesca Palandri, Ruben A. Mesa, Claire Harrison, Gautam Sajeev, Boris Gorsh, Ryan Simpson, Sang Kyu Cho, Zhaohui Wang, Catherine Elizabeth Ellis, Seán Conlon, James Signorovitch
Journal: Journal of Clinical Oncology (2023)

7065 Background: JAK inhibitors (JAKi) are a mainstay of MF treatment, with proven ability to improve symptoms and spleen volume for most pts; although safety profiles vary, some approved JAKi have associated hematologic toxicity. The JAK1/JAK2/ACVR1 inhibitor MMB has shown consistent benefit in improving anemia, symptoms, and spleen volume in pts with MF. Clinical trials have directly compared MMB with ruxolitinib, with MMB showing a more favorable hematologic toxicity profile. However, there are limited data comparing MMB vs other JAKi such as FED. We performed an ITC of safety outcomes between MMB and FED in pts with MF. Methods: A matching-adjusted indirect comparison (MAIC) was undertaken to compare outcomes from phase 2 and/or 3 MMB and FED trials. Adverse events (AEs) occurring in &gt; 10% of a treatment arm over 24 weeks were evaluated; primary outcomes were grade 3/4 anemia and thrombocytopenia. Separate analyses were performed in JAKi-naive (SIMPLIFY-1 [S1] vs JAKARTA) and JAKi-experienced (pooled SIMPLIFY-2 [S2], MOMENTUM vs JAKARTA2) pts. Evaluable outcomes were limited by published aggregate data, so not all were feasible to compare. MAIC involved reweighting MMB pt data by matching baseline characteristics prioritized by expert clinical input (DIPSS/IPSS, Total Symptom Score, platelet counts, spleen volume/length, and/or hemoglobin levels) between trial arms, and determining odds ratios (ORs), risk ratios, and risk differences (RDs) between outcomes in resulting balanced populations. As nonrandomized groups were compared, results may be biased due to unmeasured/residual confounding, despite adjusting for prognostic factors/effect modifiers. Results: Effective MMB sample sizes after adjustment were 151.1 JAKi-naive and 79.4 JAKi-experienced pts. Risk of any or grade 3/4 anemia, diarrhea, nausea, and serious AEs leading to dose reductions were statistically less likely with MMB vs FED in both populations; any or grade 3/4 thrombocytopenia was also less likely with MMB vs FED, significantly so in JAKi-naive pts. Odds/risk of other outcomes assessed varied in significance (key OR/RD results presented in the Table). No identified outcomes were statistically less likely with FED. Conclusions: MMB showed a favorable safety profile vs FED in both JAKi-naive and experienced pts, including a significantly lower risk of key hematologic AEs, diarrhea, and nausea over 24 weeks. Clinical trial information: NCT04173494 ; NCT01969838 ; NCT02101268 ; NCT01523171 ; NCT01437787 . [Table: see text]